Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0001418 (adenocarcinoma)
68,496 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The HNK-1 monoclonal antibody detects an antigen (Leu-7) on a subpopulation of large granular lymphocytes which have natural killer cell function. Recently this antigen has been found on nonhemopoietic tissues. In the present study human lung tumor cells were examined for the presence of Leu-7 antigen using an enzyme-linked immunosorbent assay, immunoperoxidase staining, and fluorescence-activated cell sorter analysis. All small cell lung tumor cells tested were Leu-7 positive. In contrast only two of seven biopsy specimens from small cell lung cancer patients were Leu-7 positive. Several large cell lung tumor lines were Leu-7 positive while an adenocarcinoma and squamous cell carcinoma were negative. These results indicate that expression of Leu-7 antigen on lung tumor cells is heterogeneous both in vitro and in vivo. Small cell lung tumor lines have been reported to undergo histological conversion in vitro accompanied by the loss of a number of biochemical markers. In our study histologically converted cells exhibited much less reactivity with HNK-1 than did the parent cells. These results indicate that the degree of expression of Leu-7 antigen may be under the control of differentiation-related events. Thus monoclonal antibody HNK-1 has been very useful in studying heterogeneity within and among lung tumor cells.
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PMID:Differential expression of the Leu-7 antigen on human lung tumor cells. 392 54

Cytogenetic analysis of six cases of ovarian adenocarcinoma revealed the presence of common marker chromosomes. The chromosomes involved in rearrangements, were #1 (four cases), #3 (six cases), #6 (two cases), and #17 (three cases). Our data support the presence of previously reported common aberrations of certain chromosomes in ovarian cancer. The presence in all six cases of a 3p- marker chromosome, previously reported as a specific abnormality in small cell lung cancer, indicates that it can also be found in other types of cancer.
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PMID:Common marker chromosomes in ovarian cancer. 397 32

Two human small cell lung carcinoma cell lines, NCI-H69 and NCI-H128, were used as alternating sources of immunogen to generate monoclonal antibodies to small cell lung carcinoma-associated antigens. BALB/c mice were sensitized with seven injections of live tumor cells, four with NCI-H69 cells and three with NCI-H128 cells. Somatic cell hybridization was performed by fusion of the immune murine splenocytes using syngeneic myeloma cells from the SP2/0 Ag14 cell line. Hybridoma colonies were screened against small cell lung carcinoma cells and normal lung fibroblasts with an enzyme-linked immunosorbent assay. Compared to animals immunized with only NCI-H69 or NCI-H128 cells, alternate immunization resulted in the generation of a significantly higher number of hybridomas that reacted selectively with both tumor cell lines. Monoclonal antibodies from two reactive hybrid clones generated by alternate immunization, SCLC 2051 and SCLC 5023, were uniformly negative to normal human tissues including lung, kidney, liver, spleen, breast, thyroid, brain, small intestine, and colon. While both monoclonal antibodies were nonreactive to paraffin-embedded, formalin-fixed, nonmalignant lung biopsies, the monoclonal antibody SCLC 5023 reacted with tumor cell infiltrates in biopsies from small cell lung carcinoma patients (14 of 14 cases positive), using the immunoperoxidase technique. This monoclonal reagent also reacted with other lung tumor cell types, including atypical carcinoid (5 of 5 positive), epidermoid (4 of 6 positive), undifferentiated and bronchoalveolar (3 of 4 cases each positive) carcinomas. By contrast, monoclonal antibody SCLC 2051 apparently identified an antigen expressed preferentially on small cell lung carcinoma cells (12 of 14 positive) and only rarely reacted with other lung tumor cell types (2 of 34 positive). Both monoclonal antibodies were negative to colon carcinoma, epidermoid carcinoma of the floor of the mouth, breast adenocarcinoma, and B- and T-cell leukemia and lymphoma cells, as determined by the enzyme-linked immunosorbent assay, indirect immunofluorescence, and immunoperoxidase techniques. These observations suggest that SCLC 2051 and SCLC 5023 may be of value in identifying tumor-associated antigens expressed in small cell and other lung carcinomas. In addition, the generation of antibody-producing cells towards common tumor-associated antigens may be enhanced by immunization with multiple tumor cell lines of the same histological type.
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PMID:Characterization of two human small cell lung carcinoma-reactive monoclonal antibodies generated by a novel immunization approach. 620 11

The present study was undertaken to evaluate the specificity of antitumor immunity to human lung cancer, measured by an in vitro assay--tube leukocyte adherence inhibition (LAI). We standardized and monitored the putative tumor antigen activity of the extracts by testing leukocytes from controls and patients with lung cancer in the Montreal General Hospital. A specific antitumor response to a lung cancer antigen was detected with coded leukocytes from 56% (20 out of 36) of patients with epidermoid lung cancer. By contrast, 4% (2 out of 53) of patients with inflammatory lung disease and none of 46 other patients with cancer metastatic to the lung or with other diagnoses had an LAI-positive result. The LAI response was inversely related to the extent of cancer: 80% (8 of 10) with Stage I, 66% (2 of 3) with Stage II, 54% (6 of 11) with localized Stage III, and 33% (4 of 12) with widespread Stage III were LAI positive. Leukocytes from patients with epidermoid, adenocarcinoma, or small cell lung cancer reacted to a common tumor antigen shared by extracts of epidermoid and small cell lung cancer. This study with coded samples from a remote hospital confirms the results of other investigators that the LAI measures an antitumor immune response to human organ-specific neoantigens.
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PMID:A coded study of antitumor immunity to human lung cancer assayed by tube leukocyte adherence inhibition. 626 45

Monoclonal antibodies with selectivity for human lung cancer were produced by immunizing BALB/c mice with an established line of human small cell lung cancer (NCI-H69) and fusing the mouse spleen cells to mouse myeloma line X63-Ag8.653. The resulting hybrid cells were initially screened by immunoautoradiography for production of antibodies that would react with NCI-H69 and another small cell lung cancer line (NCI-H128) but not its autologous B-lymphoblastoid line (NCI-H128BL). Stable monoclonal antibody-producing lines were isolated by repeated cloning. Three independently derived monoclonal antibodies, designated 525A5, 534F8, and 538F12, were found to react with three of the major types of human lung cancer (small cell, adenocarcinoma, and squamous carcinoma). They did not react with bronchioloalveolar and large cell lung cancers, myeloma, lymphomas, leukemias, osteogeneic sarcoma, mesothelioma, hypernephroma, malignant melanoma, simian virus 40-transformed human fetal lung cells, skin fibroblast lines, human B-lymphoblastoid lines, human erythrocytes, and rodent cells. Interestingly, these antibodies also bound to three out of three human neuroblastomas and two out of three breast cancers but failed to react with mouse neuroblastoma and rat pheochromocytoma. The monoclonal antibodies reacted with human small cell lung cancer tumors obtained at autopsy, but had insignificant reactions with normal human lung, liver, spleen, and skeletal muscle. We conclude that monoclonal antibodies have been generated that react with common antigenic determinants expressed on several human lung cancer types, neuroblastoma, and some breast cancers, but are not detectable by our current assays on a variety of other human tumors or normal adult human tissues. Such antibodies are of potential clinical and biological importance.
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PMID:Monoclonal antibodies that demonstrate specificity for several types of human lung cancer. 627 Jun 85

Two murine IgG2Ak monoclonal antibodies (703D4, 704A 1) were produced and characterized after immunization with a human large cell lung cancer line (NCI-H 157). These antibodies detect different epitopes on 31 kilodalton [35S]methionine incorporating protein(s). Radiobinding and immunohistochemical studies show these antibodies bind to most (11/13) human non-small cell lung cancer (adenocarcinoma, epidermoid, and large cell), but not to small cell lung cancer (0/11) tumors tested. The epitopes these antibodies recognized are also expressed on human melanomas (7/8), two other tumors (osteogenic sarcoma, renal cell carcinoma), but not on many other human tumors (breast, colon, neuroblastoma, lymphoid), and not on a panel of normal adult human tissues. Because the antigen(s) are preserved after fixation and because of their ability to distinguish lung cancer types from each other and normal tissues, they should be of clinical, as well as of biologic interest.
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PMID:Monoclonal antibodies that distinguish non-small cell from small cell lung cancer. 630 2

Etoposide (VP 16) is a semi-synthetic derivative of 4'- demethylepipodophyllotoxin , a naturally occurring compound synthesized by the North American May apple (Podophyllum peltatum ) and the Indian species Podophyllum emodi Wallich . Although podophyllotoxins are classical spindle poisons causing inhibition of mitosis by blocking mitrotubular assembly, etoposide inhibits cell cycle progression at a premitotic phase (late S and G2), probably via inhibition of DNA synthesis. There appears to be a selective antileukemic dose response relationship when compared to normal hematopoietic elements. Etoposide is effective when administered orally at about twice the recommended parenteral dosage. Schedule dependency in both animal models and clinical trials has been observed; multiple dosing over three to five consecutive days is superior to weekly single dose administration. Etoposide's dose-limiting toxicity is myelosuppression (leukopenia), which is quite predictable; alopecia and Gl toxicity (nausea, vomiting, stomatitis) occur in about 20-30% of patients given recommended dosages. Etoposide appears to be one of the most active drugs for small cell lung cancer, testicular carcinoma (the Food and Drug Administration approved indication), ANLL and malignant lymphoma. Etoposide also has demonstrated activity in refractory pediatric neoplasms, hepatocellular, esophageal, gastric and prostatic carcinoma, ovarian cancer, chronic and acute leukemias and non-small cell lung cancer, although additional single and combination drug studies are needed to substantiate these data. Its contribution in front-line combination chemotherapeutic regimens for these cancers will be better defined in the forthcoming years. Etoposide appears to have minimal activity in breast cancer and, based on current data, it is inactive against malignant melanoma, colorectal adenocarcinoma and cancer of the head and neck, although the dosage and schedules used in many of the Phase II studies may have been suboptimal.
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PMID:Etoposide: a semisynthetic epipodophyllotoxin. Chemistry, pharmacology, pharmacokinetics, adverse effects and use as an antineoplastic agent. 632 63

Ten patients with stage I-II SCLC received IC-AS between 1984 and 1993. As induction chemotherapy, COMP-VAN alternating chemotherapy and CAV-PVP hybrid chemotherapy were administered. The former consisted of a 4-drug combination of cyclophosphamide (CPA), vincristine (VCR), methotrexate (MTX) and procarbazine alternated with a 3-drug combination of etoposide (ETP), adriamycin (ADM) and nimustine every 4 weeks. In the latter, a 3-drug combination of CPA, ADM and VCR given on day 1, and a 2-drug combination of ETP and cisplatin on day 8, were repeated every 4 weeks. All the patients had an objective response, including one complete response by induction chemotherapy. Post-operative pathology revealed SCLC in 4 patients, adenocarcinoma in 2 and no tumor (pathological CR) in 4. Four patients relapsed, and a intrathoracic relapse was experienced in only 2 patients. Six patients have died: 3 from relapsing SCLC, 2 from stomach cancer, and 1 from squamous lung cancer, who was salvaged from relapsing SCLC. The median survival time was 27.5 months, and the 3-year survival rate 37.5%. These results indicate that IC-AS is highly effective for stage I-II SCLC and warrant additional studies comparing IC-AS with chemo-radiotherapy.
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PMID:[Induction chemotherapy followed by adjuvant surgery (IC-AS) in patients with stage I-II small cell lung cancer (SCLC)]. 748 26

Structural and functional analyses of several integrin heterodimers were performed in non-small-cell lung cancer (NSCLC) and small cell lung cancer (SCLC) cell lines. The expression of beta 1, beta 3, beta 4, and beta 5 heterodimers was evaluated at protein and mRNA levels. By flow cytometry and immunoprecipitation experiments we demonstrate that NSCLC cells (A549 adenocarcinoma and DG 3 large cell carcinoma) coexpress integrin heterodimers composed of beta 1, beta 3, beta 4, and beta 5 subunits, whereas SCLC cells (AE2 and H69) express only beta 1 integrin heterodimers. Northern blot experiments confirmed immunochemical analysis: SCLC cells in contrast to NSCLC cells express only the mRNA coding for the beta 1 subunit. These data indicate that in lung carcinoma cells the diversity in the integrin repertoire depends upon differential gene expression. The functionality of integrin receptors has been studied using antibody blocking experiments. Data reported demonstrate that the alpha 6 beta 1 integrin is a laminin receptor in either SCLC or NSCLC cells. An antibody to the beta 4 subunit partially inhibits the adhesion of adenocarcinoma cells to lamin but does not block lamin adhesion of large cell carcinoma cells, even though alpha 6 beta 4 complexes are expressed on both cell types. Two antisera to vitronectin receptors inhibit the adhesion of NSCLC cels to both vitronectin and fibronectin. The same antisera inhibit the adhesion of SCLC cells only to laminin, indicating that the alpha v beta 1 integrin might function in these cells as laminin receptor.
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PMID:Expression of beta 1, beta 3, beta 4, and beta 5 integrins by human lung carcinoma cells of different histotypes. 750 46

In order to analyze the presence and the function of the "insulin-like growth factor I (IGF-I) system" in human non-small-cell lung cancer (N-SCLC) we tested 5 cell lines of different histological sub-types: A549, Ca-Lu-6, SK-Lu-1 (adenocarcinoma); Ca-Lu-1, SK-Mes-1 (squamous carcinoma) and one normal fibroblast-like fetal lung cell line (IMR-90) for expression of the IGF-I peptide and its RNA transcribed from the IGF-I gene; IGF-binding proteins (IGF-BP); IGF-I receptor (IGF-I-R) and its mRNA. In addition, we examined the capacity of exogenous human recombinant IGF-I to enhance the in vitro cell proliferation. In medium conditioned from cell cultures, we detected immunoreactive IGF-I material by radioimmunoassay. Western ligand blot and affinity labelling demonstrated the presence of several molecular species of IGF-BPs (IGF-BP-4, -1, -2, -3) as well. Northern blot analysis of polyA+ RNA from all cell lines examined revealed the presence of IGF-I and IGF-I-R mRNA. Moreover, binding studies on cultured cell lines showed one class of high-affinity, operative type-I IGF cell-surface binding sites. Finally, by thymidine uptake and colorimetric metabolic MTT assays, we found that most neoplastic cell lines react mitogenically to IGF-I and that its physiological effect is abolished by an anti-IGF-I-receptor antibody. These data indicate the importance of the IGF-I system in N-SCLC growth. Furthermore, they suggest that this mitogenic complex should be appraised as a possible target for anti-neoplastic drugs, antibodies or growth-factor analogues offering potential new approaches to therapy.
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PMID:Expression and function of the insulin-like growth factor I system in human non-small-cell lung cancer and normal lung cell lines. 750 79


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